Moderation of buprenorphine therapy for cocaine dependence efficacy by variation of the Prodynorphin gene.

PURPOSE: The aim of this secondary analysis was to identify prodynorphin (PDYN) genetic markers moderating the therapeutic response to treatment of cocaine dependence with buprenorphine/naloxone (Suboxone®; BUP). METHODS: Cocaine-dependent participants (N = 302) were randomly assigned to a platform of injectable, extended-release naltrexone (XR-NTX) and one of three daily medication arms: 4 mg BUP (BUP4), 16 mg BUP (BUP16), or placebo (PLB) for 8 weeks (Parent Trial Registration: Protocol ID: NIDA-CTN-0048, Clinical Trials.gov ID: NCT01402492). DNA was obtained from 277 participants. Treatment response was determined from weeks 3 to 7 over each 1-week period by the number of cocaine-positive urines per total possible urines. RESULTS: In the cross-ancestry group, the PLB group had more cocaine-positive urines than the BUP16 group (P = 0.0021). The interactions of genetic variant × treatment were observed in the rs1022563 A-allele carrier group where the BUP16 group (N = 35) had fewer cocaine-positive urines (P = 0.0006) than did the PLB group (N = 26) and in the rs1997794 A-allele carrier group where the BUP16 group (N = 49) had fewer cocaine-positive urines (P = 0.0003) than did the PLB group (N = 58). No difference was observed in the rs1022563 GG or rs1997794 GG genotype groups between the BUP16 and PLB groups. In the African American-ancestry subgroup, only the rs1022563 A-allele carrier group was associated with treatment response. CONCLUSION: These results suggest that PDYN variants may identify patients who are best suited to treatment with XR-NTX plus buprenorphine for cocaine use disorder pharmacotherapy.

Prevalence, Diagnosis, and Treatment Rates of Mood Disorders among Opioid Users under Criminal Justice Supervision.

BACKGROUND: Individuals involved in the criminal justice system have disproportionately high rates of psychiatric disorders when compared to the general U.S. POPULATION: If left untreated, the likelihood of subsequent arrest increases and risk for adverse health consequences is great, particularly among opioid users. OBJECTIVES: To explore the prevalence, characteristics, and treatment of mood disorders among justice involved opioid-dependent populations. METHODS: The current study enrolled 258 treatment-seeking opioid-dependent individuals under community-based criminal justice supervision (e.g., probation, parole) screened from the larger parent study, Project STRIDE, a seek/test/treat randomized control trial (RCT) examining HIV and opioid use treatment. During baseline, individuals were screened for depression using the Patient Health Questionnaire-9 (PHQ-9) and screened for bipolar disorder using the Mood Disorder Questionnaire (MDQ) tool. RESULTS: Overall, 78 (30%) participants screened positive for moderate to severe depression and 54 (21%) screened positive for bipolar disorder. Participants self-reported mood disorders at higher rates than they screened positive for these conditions. Participants screening positive for these conditions experienced significantly greater family, legal, and medical problems on the Addiction Severity Index-Lite (ASI-Lite) than those who did not screen positive. Incidence of a lifetime suicide attempt was found to be associated with a positive screen for both mood disorders. Prescribed psychotropic treatment utilization was similar among those who screened positive for depression or bipolar disorder with approximately 38% reporting taking medication. IMPORTANCE: Findings suggest universal mood disorder screening to improve comprehensive psychiatric care and treatment of opioid-dependent justice-involved individuals.

Factors associated with non-adherence to Buprenorphine-naloxone among opioid dependent African-Americans: A retrospective chart review.

BACKGROUND AND OBJECTIVES: Opioid use disorders are common, chronic relapsing disorders. Buprenorphine (BUP) is an FDA approved medication in the treatment of opioid use disorders, but patient adherence to this medication remains a challenge. To identify risk factors for non-adherence, this chart review study examined the association between DSM-IV Axis I psychiatric disorders, substance use, demographics, and adherence to BUP-naloxone in African-American patients. METHODS: Charts were selected of patients who had ≥5 visits and completed psychometric screens (Patient Health Questionnaire, Mood Disorder Questionnaire, and a posttraumatic stress disorder questionnaire) at the time of the initial visit (N = 50). Urine drug screens (UDS) were also obtained. Treatment adherence was defined as BUP presence in UDS for ≥80% of the visits. RESULTS: A total of 48% of patients were adherent to treatment. Non-adherent patients had higher rates of use for not only opioids, but also cocaine, and alcohol. Cocaine use was associated with BUP-naloxone non-adherence even after controlling for opioid use. Attendance in cognitive behavioral group therapy sessions (CBT) was significantly associated with adherence. Patients endorsing PTSD symptoms showed higher adherence to treatment compared to those who did not endorse these symptoms. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Our results indicate that alcohol and illicit substance use is associated with non-adherence to BUP-naloxone treatment, and suggests that CBT and efforts to promote abstinence from non-opioid substance use may improve adherence among African-Americans. These findings contribute to growing literature on understanding adherence to BUP-naloxone, which is critical to reduce morbidity and mortality.

Genome-wide association of bipolar disorder suggests an enrichment of replicable associations in regions near genes.

Although a highly heritable and disabling disease, bipolar disorder's (BD) genetic variants have been challenging to identify. We present new genotype data for 1,190 cases and 401 controls and perform a genome-wide association study including additional samples for a total of 2,191 cases and 1,434 controls. We do not detect genome-wide significant associations for individual loci; however, across all SNPs, we show an association between the power to detect effects calculated from a previous genome-wide association study and evidence for replication (P = 1.5×10(-7)). To demonstrate that this result is not likely to be a false positive, we analyze replication rates in a large meta-analysis of height and show that, in a large enough study, associations replicate as a function of power, approaching a linear relationship. Within BD, SNPs near exons exhibit a greater probability of replication, supporting an enrichment of reproducible associations near functional regions of genes. These results indicate that there is likely common genetic variation associated with BD near exons (±10 kb) that could be identified in larger studies and, further, provide a framework for assessing the potential for replication when combining results from multiple studies.

Impact of a psychoeducational intervention on willingness to seek help for depression among African American young adults.

Despite the success of psychoeducational interventions at improving willingness to seek professional help for mental illness, limited research explores the effect of culturally tailored psychoeducational interventions on African American (AA) college students. The objective of this study was to determine if exposure to a culturally relevant psychoeducational intervention impacted AA young adult attitudes, subjective norms, perceived behavioral control, depression stigma, disclosure and willingness to seek help for depression. We conducted a one-group pre- and post-test intervention study of AA college students (N = 75). The 2.5-h intervention featured presentations, large-group discussions, videos, and active learning exercises and was guided by applying a cultural adaptation framework to an existing psychoeducational intervention. The self-administered surveys were created using the Theory of Planned Behavior as a guide. Data were analyzed using paired t-tests. A total of 70 participants completed both pre- and post-test surveys. Overall, willingness, attitude, and disclosure significantly increased after the intervention (p < .001). Additionally, depression stigma significantly decreased after the intervention, indicating fewer stigmatizing beliefs about depression (p < .001). Willingness to seek help for depression among AA college students can be improved through culturally relevant and interactive psychoeducational interventions. These interventions can also improve negative attitudes and perceived behavioral control toward seeking help and decrease stigmatizing beliefs. More research is needed to explore the longitudinal impact of culturally relevant psychoeducational interventions and how they may affect actual help-seeking behavior among AA college students.

Mental health of African Americans and Caribbean blacks in the United States: results from the National Epidemiological Survey on Alcohol and Related Conditions.

OBJECTIVES: Previous epidemiological studies have found lower mood, anxiety, and substance use disorder prevalence in Black Americans, in general, compared with White Americans. We estimated the prevalence and persistence of psychiatric disorders in African Americans, Caribbean Blacks, and non-Hispanic Whites. METHODS: We drew data from wave 1 (2001-2002) of the National Epidemiological Survey of Alcohol and Related Conditions, a nationally representative sample of US adults, which included 7529 African Americans, 469 Caribbean Blacks, and 24 502 non-Hispanic Whites. RESULTS: Blacks had equal or lower prevalence than Whites of lifetime (adjusted odds ratio [AOR] =0.6 for African Americans; 0.3 for Caribbean Blacks) and 12-month (AOR =0.7 for African Americans; 0.4 for Caribbean Blacks) Axis I psychiatric disorders, but higher prevalence of several personality disorders. Among Blacks, Caribbean Blacks had higher prevalence of 12-month psychotic disorders and lower lifetime prevalence of major depressive disorder, alcohol dependence, and drug abuse than African Americans. There were no differences in persistence of disorders between Caribbean Blacks and African Americans. CONCLUSIONS: This study yielded new data on prevalence of mental disorders in these groups, which has important implications for clinical work with US Blacks.

Evidence for association of bipolar disorder to haplotypes in the 22q12.3 region near the genes stargazin, IFT27 and parvalbumin.

We have previously reported genome-wide significant linkage of bipolar disorder to a region on 22q12.3 near the marker D22S278. Towards identifying the susceptibility gene, we have conducted a fine-mapping association study of the region in two independent family samples, an independent case-control sample and a genome-wide association dataset. Two hundred SNPs were first examined in a 5 Mb region surrounding the D22S278 marker in a sample of 169 families and analyzed using PLINK. The peak of association was a haplotype near the genes stargazin (CACNG2), intraflagellar transport protein homolog 27 (IFT27) and parvalbumin (PVALB; P = 4.69 × 10(-4)). This peak overlapped a significant haplotype in a family based association study of a second independent sample of 294 families (P = 1.42 × 10(-5)). Analysis of the combined family sample yielded statistically significant evidence of association to a rare three SNP haplotype in the gene IFT27 (P = 8.89 × 10(-6)). Twelve SNPs comprising these haplotypes were genotyped in an independent sample of 574 bipolar I cases and 550 controls. Statistically significant association was found for a haplotype window that overlapped the region from the first two family samples (P = 3.43 × 10(-4)). However, analyses of the two family samples using the program LAMP, found no evidence for association in this region, but did yield significant evidence for association to a haplotype 3' of CACNG2 (P = 1.76 × 10(-6)). Furthermore, no evidence for association was found in a large genome-wide association dataset. The replication of association to overlapping haplotypes in three independent datasets suggests the presence of a bipolar disorder susceptibility gene in this region.

PTSD treatment of African American adults in primary care: the gap between current practice and evidence-based treatment guidelines.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a common, potentially disabling, underdiagnosed, and under-treated illness. Primary care physicians assume a critical role in the diagnosis, treatment, and referral of African Americans with PTSD since mental health access is limited for this population. This study is an examination of PTSD treatment of African Americans in the primary care setting. Actual treatment provision is contrasted with existing evidence-based PTSD treatment guidelines. METHOD: Researchers screened 738 consenting, mostly African American, adults in 4 academically affiliated primary care offices for both trauma exposure and mental health symptoms, including PTSD. RESULTS: Employing criteria from the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) (DSM-IV), investigators diagnosed 91 of the participants with current PTSD using the Structured Clinical Interview for DSM and the clinician-administered of PTSD Scale for DSM-IV. Treatment statistics include: 69.2% (n=63) had never received treatment from a mental health provider: 18.6% (n=17) were currently seeing a mental health practitioner; nearly half (47.9%, n=24) of a subsample had never discussed traumatic event exposure or mental health symptoms with their primary care doctor; 32% (n=29) were prescribed psychotropic medication and only 18.6% (n=17) were participating in any form of psychotherapy. Concurrent psychiatric disorders were found in 46.2% (n = 42) of the participants with PTSD. CONCLUSION: Most African American adult primary care patients with PTSD were either undiagnosed or undertreated in this inner-city setting. These results demonstrate a clear need to improve screening and treatment services. Both individual (provider and patient) and system-based changes will be required to meet the demonstrated clinical need.